Smoking

In view of reports that smoking might reduce the expression of HLA-D region antigens, the results for the 25 nonsmokers in the EAA and sarcoidosis groups were compared with those for the six nonsmokers with FA (CFA or scleroderma). This confirmed that the intensity of expression especially of HLA-DQ (p<0.05), but also of HLA-DR, DP, and transferrin receptors, was higher in the patients with granulom­atous compared with fibrosing lung diseases. Further­more, the results for the 25 nonsmokers resembled those for the 11 current or exsmokers in the EAA and sarcoidosis groups.

Relationships with Lymphocytes and their Subpopulations Present in the Lavage Samples

Increased numbers of lymphocytes were observed in the lavage samples of the patients with EAA and sarcoidosis (Table 2). In sarcoidosis (Table 4), the numbers of lymphocytes per milliliter and their per­centage counts in the lavage fluids of the patients showed a significant correlation with the intensity of all four alveolar macrophage surface markers studied. The closest correlations were with HLA-DP (r= .83, p<0.001 and r=.69, p<0.005 for lymphocytes per milliliter and percent, respectively) and HLA-DQ (r= .61, p<0.005 and r= .51, p<0.01, respectively).
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In sarcoidosis there were also significant correlations between the intensity of alveolar macrophage surface markers and counts of T-cell subsets (Table 4). In particular, percentages of helper T cells correlated most closely with HLA-DR (rs=.54, p<0.005) and also showed a trend of correlation with HLA-DP and transferrin receptors. By contrast, no significant cor­relations were observed between T-cell subsets and HLA-DQ levels.

BAL lymphocyte activation was evaluated by deter­mining the percentages of lymphocytes expressing receptors for interleukin 2 and by measuring the DNA content of the lymphocytes using PI and flow cytom­etry. There was a significant correlation between the percentages of lymphocytes in the S + G2 + M phase of the cell cycle and the intensity of HLA-DQ on alveolar macrophages in the patients with sarcoidosis (rs=.36, p<0.05) (Table 4). These correlations were not observed in the patients with EAA.

Correlations with Lung Function Measurements

Correlations were undertaken to explore whether the increased expression of surface receptors on alveolar macrophages showed any relationship with lung function measurements conducted the day before lavage in the patients with EAA and sarcoidosis.

In the patients with sarcoidosis (Table 5), there was a significant inverse correlation between decreasing

Deo, FVC, and TLC values (mean percent predicted) and increasing intensity of HLA-DQ on the alveolar macrophages (rs= — .48, p<0.025; rs= — .43, p<0.025; rs= — .36, p<0.05, respectively). There were also trends (p<0.1) of inverse correlation with the intensity of HLA-DP.

Table 4—Correlations Between Levels of Alveolar Macrophage Surface Markers and BAL Lymphocyte Subpopulations in Patients with Sarcoidosis

Lymphocytes

Alveolar Macrophages Relative Median Fluorescent Intensity (Total
Cells) of:

HLA-DR*

HLA-DQ*

HLA-DPt

Trans-Rec*

r„

P

r,

P

r,

P

r,

P

Counts

BAL lymphs per ml

.28

<.10

.61

<.005

.83

<.001

.37

<.05

BAL lymphs %

•42

<.025

.51

<.01

.69

<.005

.45

<.025

Subsets

%B

.09

.17

-.11

-.12

%T

.67

<.001

.24

.67

<.01

.40

<.05

% T-helper/inducer

.54

<.005

.24

.48

<.10

.32

<.10

% T-suppressor/cytotoxic

-.22

-.14

-.52

<.05

-.26

THI:TSC ratio

.44

<.025

.19

.52

<.05

.40

<.05

Activation markers

% IL-2-REC

-.10

-.23

-.05

.08

% L4n tetraploid cells

.09

.36

<.05

.34

.003

Contrasting Features Compared with Blood Monocytes

Our results confirm that, while the majority of blood monocytes express HLA-DR antigens (median, 73 percent; range, 58 to 87 percent; mean±SD, 74 ± 10 percent), significantly lower percentages express HLA-DQ (median, 5 percent; range, 0 to 25 percent; mean±SD, 9±9 percent) and HLA-DP (median, 17 percent; range, 0 to 28 percent; mean±SD, 17 ±8 percent; p<0.005, Mann-Whitney U test). This con­trasts with our findings that HLA-DQ and DP as well as HLA-DR antigens are detectable on the majority of alveolar macrophages (Table 3).
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Table 5—Correlations Between Levels of Alveolar Macrophage Surface Markers and Lung Function Measurements tn Patients with Sarcoidosis

Lung Function

Alveolar Macrophages Relative Median Fluorescent Intensity (Total
Cells) of:

Trans-Rec*

HLA-DR*

HLA-DQ

*

HLA-DPt

r. P

r,

P

r,

P

r. P

Mean % predicted

Deo

-.03

-.48

<.025

-.46

<.10

-.02

KCO

.04

-.12

-.25

-.03

FVC

-.05

-.43

<.025

-.39

<.10

-.07

FEV,

-.18

-.56

<.005

-.40

<.10

-.27

TLC

.05

-.36

<.05

-.32

-.02

Transferrin receptors were also expressed on only a minority of blood monocytes (median, 6 percent; range, 0 to 9 percent; mean±SD, 6±3 percent), contrasting with the findings for alveolar macrophages (Table 3).