PMID- 1918986
OWN - NLM
STAT- MEDLINE
DCOM- 19911118
LR  - 20161019
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 147
IP  - 8
DP  - 1991 Oct 15
TI  - A role for transforming growth factor-beta 1 in regulating natural killer cell 
      and T lymphocyte proliferative responses during acute infection with lymphocytic 
      choriomeningitis virus.
PG  - 2717-27
AB  - The role of transforming growth factor beta 1 (TGF-beta 1) in regulating NK and T 
      cell proliferation during acute viral infections was investigated. After 
      infection of mice with lymphocytic choriomeningitis virus, NK cell proliferation 
      peaks on day 3 and subsides by days 5 to 7 postinfection, whereas T cell 
      proliferation peaks on day 7 and declines by days 9 to 14 postinfection. As 
      TGF-beta 1 has been shown to inhibit lymphocyte proliferation in culture, the 
      production and function of TGF-beta 1 during infection was evaluated in this 
      model. Northern blot analysis demonstrated that the accumulation of TGF-beta 1 
      transcripts remained relatively constant in total splenic leukocytes during 
      infection. The Mv 1 Lu mink lung cell bioassay was modified and used to evaluate 
      the production of biologically active TGF-beta 1 during infection. Media 
      conditioned with splenic leukocytes isolated from infected mice contained factors 
      that inhibited DNA synthesis by the Mv 1 Lu cells. Low levels of inhibition were 
      observed with conditioned media prepared on day 3 postinfection and high levels 
      of inhibition were observed with conditioned media prepared on days 5 through 14 
      postinfection. Neutralization with antibodies specific for TGF-beta 1 
      demonstrated that TGF-beta 1 contributed to the inhibitory activity. As TGF-beta 
      1 was produced at times coinciding with the decline in NK cell proliferation, the 
      TGF-beta 1 sensitivity of in vivo-elicited NK cells was evaluated. In vitro and 
      in vivo studies demonstrated that NK cell proliferation was extremely sensitive 
      to inhibition by TGF-beta 1. In culture, TGF-beta 1 had an ID50 of 8 pg/ml for 
      inhibiting DNA synthesis by blast NK cells. In vivo, administration of a total of 
      0.18 micrograms of TGF-beta 1 resulted in a 93% inhibition of NK cell-mediated 
      lytic units per spleen on day 3 postinfection. The inhibition was a result of a 
      block in NK cell proliferation, as administration of TGF-beta 1 profoundly 
      suppressed the appearance of blast size NK cells and the incorporation of [3H] 
      thymidine by NK cell-enriched, blast lymphocyte populations on day 3 
      postinfection. In contrast to NK cell proliferation, T cell proliferation was not 
      inhibited by up to 100-fold higher concentrations of the factor in vitro or in 
      vivo. Taken together, these data demonstrate that TGF-beta 1 is an important 
      regulator of NK cell proliferation in vivo. Furthermore, the results indicate 
      that differential sensitivity to TGF-beta 1 may contribute to the coordination of 
      NK and T cell responses during viral infections.
FAU - Su, H C
AU  - Su HC
AD  - Division of Biology and Medicine, Brown University, Providence, RI 02912.
FAU - Leite-Morris, K A
AU  - Leite-Morris KA
FAU - Braun, L
AU  - Braun L
FAU - Biron, C A
AU  - Biron CA
LA  - eng
GR  - R01 CA041268/CA/NCI NIH HHS/United States
GR  - CA-41268/CA/NCI NIH HHS/United States
GR  - CA-46617/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Killer Cells, Natural/*immunology
MH  - *Lymphocyte Activation
MH  - Lymphocytic Choriomeningitis/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - RNA, Messenger/analysis
MH  - T-Lymphocytes/*immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transforming Growth Factor beta/genetics/pharmacology/*physiology
EDAT- 1991/10/15 00:00
MHDA- 1991/10/15 00:01
CRDT- 1991/10/15 00:00
PHST- 1991/10/15 00:00 [pubmed]
PHST- 1991/10/15 00:01 [medline]
PHST- 1991/10/15 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1991 Oct 15;147(8):2717-27.