Whitmire J K, Murali-Krishna K, Altman J, Ahmed R
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Philos Trans R Soc Lond B Biol Sci. 2000 Mar 29;355(1395):373-9. doi: 10.1098/rstb.2000.0577.
Following acute lymphocytic choriomeningitis virus (LCMV) infection, there is a potent antiviral CD8 T-cell response that eliminates the infection. This initial CD8 T-cell response is followed by a period of memory during which elevated numbers of virus-specific CD8 T cells remain in the mouse. CD4 T cells are also activated after LCMV infection, but relatively less is known about the magnitude and duration of the CD4 response. In this study, we used intracellular staining for interferon-gamma to measure both CD4 and CD8 responses in the same mice at the single cell level. After LCMV infection, there was an increase in the number of activated CD4 T cells and an associated increase in the number of virus-specific CD4 T cells. At the peak of this expansion phase, the frequency of virus-specific CD4 T cells was 1 in 20 (0.5-1.0 x 10(6) per spleen). Like the CD8 response, long-term CD4 memory could be found up to a year after the infection with frequencies of approximately 1 in 260 (0.5-1.5 x 10(5) per spleen). However, the magnitude of virus-specific CD8 T cells was greater than virus-specific CD4 T cells during all phases of the immune response (expansion, death, and memory). At day 8, there were 20- to 35-fold more virus-specific CD8 T cells than CD4 T cells. This initial difference in cell number lasted into the memory phase as there remained a ten- to 20-fold difference in the CD8 and CD4 responses. These results highlight the importance of the expansion phase in determining the size of the memory T-cell pool. In addition to the difference in the magnitude, the activation requirements of CD8 and CD4 T-cell responses were different: CD8 T responses were not affected by blockade of CD40-CD40 ligand interaction whereas CD4 responses were reduced 90%. So while there is long-term memory in both the CD8 and CD4 compartments, the rules regulating the activation of CD8 and CD4 T cells and the overall magnitude of the responses are different.
感染急性淋巴细胞性脉络丛脑膜炎病毒（LCMV）后，会产生有效的抗病毒CD8 T细胞应答，从而消除感染。这种初始的CD8 T细胞应答之后会进入记忆期，在此期间，小鼠体内病毒特异性CD8 T细胞数量会增加。LCMV感染后CD4 T细胞也会被激活，但关于CD4应答的强度和持续时间，人们了解得相对较少。在本研究中，我们使用细胞内γ干扰素染色法在单细胞水平上测量同一小鼠体内的CD4和CD8应答。LCMV感染后，活化的CD4 T细胞数量增加，同时病毒特异性CD4 T细胞数量也相应增加。在这个扩增阶段的高峰期，病毒特异性CD4 T细胞的频率为20个中有1个（每个脾脏0.5 - 1.0×10⁶个）。与CD8应答一样，感染后长达一年都能发现长期的CD4记忆，频率约为260个中有1个（每个脾脏0.5 - 1.5×10⁵个）。然而，在免疫应答的所有阶段（扩增、死亡和记忆），病毒特异性CD8 T细胞的数量都多于病毒特异性CD4 T细胞。在第8天，病毒特异性CD8 T细胞比CD4 T细胞多20到35倍。细胞数量的这种初始差异一直持续到记忆期，因为CD8和CD4应答之间仍然存在10到20倍的差异。这些结果突出了扩增阶段在决定记忆性T细胞库大小方面的重要性。除了数量上的差异，CD8和CD4 T细胞应答的活化要求也不同：CD8 T应答不受CD40 - CD40配体相互作用阻断的影响，而CD4应答则降低了90%。所以虽然CD8和CD4区室都存在长期记忆，但调节CD8和CD4 T细胞活化的规则以及应答的总体强度是不同的。
