Photoimmunology -Past, Present and Future-

Daynes, Raymond A.,Chung, Hun-Taeg,Roberts, Lee K. The Korea Society for Microbiology 1986 大韓微生物學會誌 Vol.21 No.3

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral

Murine lymphokines production in lymphoid organs during the various stages of lactation

류시윤,Ryu, Si-yun,Daynes, Raymond A. The Korean Society of Veterinary Science 1994 大韓獸醫學會誌 Vol.34 No.1

비유중기, 건유초기 및 임신말기의 C3H/HeN 마우스의 비장, 장간막림프절, 말초림프절(액와, 상완 및 샅림프절)유래 림프구에서 생산되는 lymphokine의 양을 비교하였다. 비장에서의 IL-2 생산양은 임신말기와 비유중기에 낮았지만, IL-4, IL-6와 $IFN_{\gamma}$의 생산양은 임신말기와 건유초기에 높았다. 말초림프절에서의 IL-4, IL-6 및 $IFN_{\gamma}$ 생산양은 임신말기와 건유초기에 높았지만, IL-2의 생산양은 임신말기, 비유중기 및 건유초기에 각각 감소하였다. 장간막림프절에서의 IL-4 생산양은 임신말기와 비유중기에 각각 증가하였으나, IL-2의 생산양은 임신말기에 감소하였다. 이와같이 전반적으로 건유초기와 임신말기에 IL-2의 생산양은 낮지만, IL-4, IL-6와 $IFN_{\gamma}$의 생산양이 높은 결과는 이 시기에 유방염의 발생비율이 높은 것과 연관성이 있는 것으로 추정된다.

Photoimmunology : Past , Present and Future

Chung, Hun Taeg,Raymond A . Daynes,Lee K . Roberts 대한미생물학회 1986 大韓微生物學會誌 Vol.21 No.3

The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a nu- mber of well-described changes in the recipients immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayed-type (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms res- ponsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviatioris io systernic antigen presenting cell (APC) potential, 4) changes in the prod- uction of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, eauses a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a 3.0cm area of skin was physically protected from the light energy. Contact sensitization of these animals with DN-FB, to either the irradiated or protected hack skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to protected dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/ m) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated a1tered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal Devels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitizetion took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes, Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent bloek of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppr essor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skins APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altcred graftversus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

Elucidation of the Mechanisms Responsible for the Immunomodulatory Influences of Ultraviolet Radiation

Chung, Hun-Taeg,Kang, Eun-Mi,Kang, Kyoung-Sook,Kim, Burnham,Lee, K. Roberts,Daynes, Raymond A. 圓光大學校 醫科學硏究所 1985 圓光醫科學 Vol.1 No.2

본 실험에서 저자들은 자외선조사에 의한 접촉성과민반응의 감소가 두 기전에 의한다는 사실을 시사하는 결과를 얻은 바 그 하나는 자외선조사에 의하여 피부의 Langerhans 씨 세포에 기능적 장애가 초래되는 것이고 다른 하나는 자외선 조사에 의한 prostaglandin 생산의 과잉으로 인한 임파구 재순환의 장애에 의한 것이다. 전자는 소량의 자외선 조사에 의한 국부적인 접촉성과민반응의 감소를 초래하나 후자는 대량의 자외선 조사에 의한 전신적 면역억제현상을 유도하며 이러한 현상은 prostaglandin 합성 억제제인 indomethacin을 투여할 경우 나타나지 아니하였다. The exposure of experimental animals to ultraviolet radiation (UVR) results in a marked reduction in their capacity to elicit contact hypersensitivity (CH) responses to epicutaneously applied skin reactive chemicals. Mice exposed to low-dose UVR (4 × 400 J/m^2/day) demonstrate a reduction in contact sensitization potential which is site specific (localized to the skin areas of direct UVR exposure) whereas high-dose exposure of mice to UVR (1 × 30,000 J/m^2) causes systemic alterations which leave the animals hyporesponsive to CH induction regardless of the skin site of hapten application. Both types of UVR-mediated alterations have been reported to associate with suppressor T-cell induction, a regulatory response which has been concluded to be responsible for the observed hyporesponsiveness to stimulation of CH reactions. Herein we report that the ability of UVR exposure to alter a recipient's capacity to elicit CH responses is mediated through two distinct mechanisms, one of which can be overridden by an inhibition of in situ prostaglandin biosynthesis by treatment with the drug indomethacin. The capacity of UVR to functionally inactivate epidermal Langerhans cells (LC) results in a markedly reduced capacity of animals that are contact sensitized directly through irradiated skin sites to elicit CH responses. This condition is associated with a lack of CH effector cells in the peripheral lymph nodes, an enhanced splenic suppressor cell activity, and cannot be reversed by indomethacin treatment. The “systemic suppression” of CH responsiveness observed in high-dose UVR-exposed animals that are sensitized through unirradiated or UVR-protected skin sites (normal LC) was found to be totaly reversible with indomethacin treatment. The mechanism responsible for the indomethacin-sensitive immunomo-dulatory effects of UVR-exposure appears to be due to the capacity of prostaglandins to sequester lymphocytes within peripheral lymph nodes via an efferent lymphatic blockade. This hypothesis was supported by our observation of a marked CH-effector cell activity in the peripheral lymph nodes of contact sensitized high-dose UVR-exposed animals which demonstrated a simultaneous presence of splenic suppressor cells. Therefore, UVR does not appear to exert its immunoregulatory activities via the preferential induction of suppressor cell activity following skin sensitization. Rather, the suppressor circuit in UVR-exposed animals appears to remain normal, with the immune modifying influences of this physical agent being due to either an inhibition of CH-effector cell generation (due to direct LC inactivation) or to a prostaglandin-mediated sequestration of CH-effector cells within peripheral lymph nodes (efferent blockade).

자외선 조사에 의한 접촉 과민 반응의 억제 기전

최점열 ( Jum Yul Choi ),손형선 ( Hyung Sun Sohn ),박석돈 ( Seok Don Park ),정헌택 ( Hun Taeg Chung ),( Raymond A. Daynes ) 대한피부과학회 1987 대한피부과학회지 Vol.25 No.5

Normal C3H/HeN strain mice exposed to low-dose ultraviolet radiation(4 * 400 J/m) demonstrated a reduction in contact sensitization potential which locaiized to the skin area of direct UVR exposure(local suppression), where high-dose exposure of UVR(1*30.000 J/m) caused systemic suppression of CH induction, regardless of the application site of 2,4-dinitro-l-fluorobenzene(DNFB). There seemed to be two different mechanisms that are responsible for CH reaction induced by UVR. One of them, local suppression of low-dose UVR resulted from blocking the afferent phase of immune response by the functiona] inactivation of the epidermal Langerhans cells ; it was associated with lack of CH effector cells in the peripheral lymph nodes, an enhanced splenic suppressor cell acitvity, and could not be reversed by indomethacin treatment. The other, systemic suppression of high-dose UVR was mediated by enhancement of prostaglandin E(PGE); it was associated with prevention of the egress of effector cells within the regional lymph node which was caused by blocking the efferent lymphatics, and elevated plasma level of PGE. And depressed CH response was reversed when treated by indomethacin.

DUAL EFFECTS OF PERTUSSIS TOXIN ON MURINE NEUTROPHILS IN VIVO

SUHN-YOUNG IM,SUSAN E. WIEDMEIER,BAIK-HWAN CHO,DONG GEUN LEE,MARYAM BEIGI,RAYMOND A. DAYNES 대한외과학회 1990 대한외과학회 학술대회 초록집 Vol.1990 No.4

마우스 동계골수이식 후 면역체계의 재생 : 1. 말초혈액 및 림프장기 세포의 숫적 변화와 림프구아군의 분포

김성호 ( Sung Ho Kim ),오헌 ( Heon Oh ),이송은 ( Song Eun Lee ),김순태 ( Soon Tae Kim ),조성기 ( Sung Kee Jo ),현병화 ( Byung Hwa Hyun ),류시윤 ( Si Yun Ryu ),( Raymond A . Daynes ) 한국수의병리학회 1997 한국수의병리학회지 Vol.1 No.1

마우스 동계골수이식 후 면역체계의 재생: I. 말초혈액 및 림프장기 세포의 숫적 변 화와 림프구아군의 분포

김성호,오헌,이송은,김순태,조성기,현병화,류시윤,Kim, Sung-Ho,Oh, Heon,Lee, Song-Eun,Kim, Soon-Tae,Jo, Sung-Kee,Hyun, Byung-Hwa,Ryu, Si-Yun,Daynes, Raymond A. 한국수의병리학회 1997 한국수의병리학회지 Vol.1 No.1

The cellularity and composition of the spleen lymph node thymus and peripheral blood and tempo of regeneration were studied at various time points after syngeneic bone marrow transplantation(BMT) in C3H/Hen mice. Significant depression of absolute lymphocyte count was noted on week 1 after lethal whole-body irradiation and BMT. In comparison to the lymph node thymus and spleen had an rapid regeneration of cellularity. The distinct cell populations($CD4^+,\;CD8^+,\;CD28^+,\;B220^+) have determined in the lymphoid tissue of mice subjected to irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated control. $CD4^+\;and\;CD8^+$ cells were present in very low numbers whereas the $B220^+$ cells reached more than normal range at 2 weeks after BMT. The number of $CD4^+$ cells returned to normal relatively soon than $CD8^+$ cell. At week 4 after BMT, the cellularity and composition of spleen lymph node and peripheral blood lymphocyte reached about 50% of the normal range therefore we can choose this time point for the other tests of immune function after BMT.