인간유두종 바이러스 감염증으로 인한 환자의 신체적 정신적 고통 및 사회경제적 비용을 감소시키기 위한 T 세포를 이용한 면역치료법의 개발을 시행하고자 하였다. 인간유두종바이러스(Human papillomavirus, HPV)에 의해 감염으로 발생하는 첨형콘딜로마(condyloma acuminata)의 조직에서 T 세포를 분리하였다. 재발 병변에 비해 초발 병변에서 분리된 T 세포에서 높은 CD4/CD8 ratio를 보였다. CD4 T 세포는 초발 병변인 경우에 분열도 더 많이하고 T 세포 내에서 비율이 더 많으나, 활성화 정도나 세포
인간유두종 바이러스 감염증으로 인한 환자의 신체적 정신적 고통 및 사회경제적 비용을 감소시키기 위한 T 세포를 이용한 면역치료법의 개발을 시행하고자 하였다. 인간유두종바이러스(Human papillomavirus, HPV)에 의해 감염으로 발생하는 첨형콘딜로마(condyloma acuminata)의 조직에서 T 세포를 분리하였다. 재발 병변에 비해 초발 병변에서 분리된 T 세포에서 높은 CD4/CD8 ratio를 보였다. CD4 T 세포는 초발 병변인 경우에 분열도 더 많이하고 T 세포 내에서 비율이 더 많으나, 활성화 정도나 세포독성기능이 증가되어 있지 않은 반면, 재발 병변의 경우에 T 세포 내 비율이 적어지지만, 활성도나 세포독성기능이 증가하였다. CD8 T 세포의 활성도와 기능이 초발 병변에서 강하고, CD4 T 세포의 활성도는 초발 병변보다는 재발에서 강하지만, 그 숫자와 분열은 초발 병변에서 증가되어 있었다. 초발 병변에서는, CD4 T 세포의 ‘ help'를 잘 받아 CD8 T 세포의 기능이 잘 유지되지만, 재발 병변에서는 CD8 T 세포가 소모되어 CD4 T 세포가 직접 effector 역할을 하는 것 같다.
Abstract▼
Human papilloma virus (HPV) infection is a rarely lethal but highly prevalent disease worldwide. Condyloma accuminata (CA), commonly known as genital warts, are a very disturbing public health problem because their prevalence seems to increase steadily around the world and the cost for treating t
Human papilloma virus (HPV) infection is a rarely lethal but highly prevalent disease worldwide. Condyloma accuminata (CA), commonly known as genital warts, are a very disturbing public health problem because their prevalence seems to increase steadily around the world and the cost for treating them are significantly high. Furthermore, prevalence of CA in Korea was reported to be much higher than that in Western countries. To reduce the burden of those patients suffers from HPV, and of the overloaded medical expenses of the society, we studied to develop effective and definite treatment option such as immunotherapy, rather than a surgical or chemical elimination because there are lots of cases recurs frequently and locates in site where they are technically difficult to be removed. In this study, we hypothesized that in the recurrent CA specimen, T cell activity might be functionally weakened than in the initial CA specimen, and which caused the recurrence. We separated and compared T cells between the specimen of recurrent group of CA and in the initial group of CA, and we explored the CD4 and CD8 T cell activities and characteristics. CD4/CD8 ratio was higher in the recurrent group. Bcl-2 expression of CD4 T cell was not different between the two groups. Granzyme B, CD69, PD-1 was expressed more in the recurrent groups, however the difference was not statistically significant. These findings showed that CD4 T cell divides more frequently and the CD4/CD8 ratio is higher but, their activity and cytotoxicity was not increased in the initial CA specimen. However, in the recurrent group, the acitiviy and cytotoxicity increased although the T cell ratio decreased in the cell. On the contrary, the ratio of CD 8 T cell presenting the Granzyme B was significantly increased in the initial group. Ki-67, the proliferation marker, and Bcl-2, the anti-apoptotic marker, increased in the CD8 T cell of the initial group. CD8 T cell presenting CD69 and PD-1(fatigue marker) were also increased in the initial group. These findings showed that antiviral activity of CD8 T cell was superior in the initial group. In other words, CD8 T cell activity and its function were stronger in the initial group, however and CD4 T cell activity was stronger in the recurrent group although its number and proliferation was increased in the initial group. Therefore, we infer that CD4 T cell number maintains and support the CD8 T cell activity in the initial infection, but it frays as it acts directly because of the decreased function of CD8 T cell in the recurrent infection. In conclusion, CD8 T cell function maintains well in the initial infection but it get damaged in the recurrent infection. On the contrary, CD4 T cell seems to proliferate well and its ratio is higher in the initial infection but do not acts as a direct effector. It rather does function properly and shows higher activity in the recurrent infection. More studies are warranted to evaulate the interaction between CD4 and CD8 T cells. We hope that this study could be helpful to develop a immunotherapeutic strategy to enforce the function of T cells enough to resist effectively the HPV viruses and to irradicate them.
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